Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

Zhang, Qiangnu; Qian, Cheng; Xia, Mengna; Huang, Xuan; Xu, He; Liao, Juan

doi:10.3389/fonc.2020.00998

Cited by 39 publications

(25 citation statements)

References 38 publications

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“…In the process of melanoma cancer, an aberrant activation of the Wnt/β-catenin signaling pathway can be found (25,26). Nevertheless, UCK2 has an uncertain relationship with the Wnt/β-catenin pathway in melanoma.…”

Section: T H E P Y R I M I D I N E R I B O N U C L E O T I D E K I N a S E U C K 2 Can Catalyze Phosphorylation Of Uridine-to-uridine Monmentioning

confidence: 99%

METTL3-induced UCK2 m6A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway

Jia

et al. 2021

Ann Transl Med

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Background: Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (m 6 A) modification is involved in a variety of biological processes, including tumorigenesis. m 6 A modifications regulate the fate and functions of RNA, such as mRNA stability, nuclear processing, transport, localization, translation, primary microRNA (miRNA) processing, and RNA-protein interactions. Several members (including METTL3, METTL14, FTO, ALKBH5, and YTHDF2) are actively involved in a variety of human cancers. However, the basic mechanism of the involvement of uridine cytidine kinase 2 (UCK2) in melanoma metastasis has not been studied. UCK2 is upregulated in a variety of malignancies. However, the complex molecular mechanisms and therapeutic effects of UCK2 in melanoma remain unclear.Methods: The expression of UCK2 was evaluated by qRT-PCR. The effects of UCK2 on the biological characteristics of PC cells were investigated on the basis of loss-of-function analyses. Immunoprecipitation-qPCR (MeRIP-qPCR) was performed to identify the m 6 A targeted effect of UCK2 in melanoma cancer.Results: Based on the bioinformatics analysis in this study, up-regulation of UCK2 could be essential in melanoma cancer, and associated with poor survival. Furthermore, the m 6 A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/β-catenin pathway. Conclusion:In this study, we found that m 6 A-METTL3 axis induced abnormal UCK2 expression plays a role in melanoma metastasis by enhancing the Wnt/β-catenin pathway, which may provide new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.

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Section: T H E P Y R I M I D I N E R I B O N U C L E O T I D E K I N a S E U C K 2 Can Catalyze Phosphorylation Of Uridine-to-uridine Monmentioning

confidence: 99%

METTL3-induced UCK2 m6A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway

Jia

et al. 2021

Ann Transl Med

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“…Specifically, activation of LncRNA-NEAT1 (another architectural component of nuclear paraspeckles) in response to hypoxia has been reported [27]. In vitro studies have demonstrated that HIF1α regulates LncRNA-NEAT1 transcription, maintaining cancer cell growth and inhibiting their apoptosis and cell cycle arrest [28]. The potential contribution of hypoxia to PSPC1 expression could be relevant in tumor cells, given that hypoxia is a common characteristic of the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea

Díaz‐García

García-Tovar

Casitas

et al. 2021

Cancers

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As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA.

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“…Therefore, miRNAs in different tumors may have different functions. In hypoxia-induced HCC, miR-199a-3p [30], miR-512-3p [31], miR-3677-3p [32], and miR-140 [33] have been found to be aberrantly expressed. Although miR-3156-5p's expression and role in HCC have not been investigated, it is highly expressed in breast cancer tissues [11] and colorectal cancer tissues [34] and is associated with malignant tumor development.…”

Section: Discussionmentioning

confidence: 99%

miR-3156-5p Enhances Hypoxia-Induced Angiogenesis in Hepatocellular Carcinoma via Modulating the SOCS5/HIF-1α/VEGF Pathway

Tie¹,

Guo²,

Li³

et al. 2021

Preprint

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Background: MicroRNAs (miRNAs) are dysregulated in hypoxia-induced hepatocellular carcinoma (HCC). This study probed the regulatory mechanism of miR-3156-5p on HCC under hypoxia. Methods: HCC cells (HepG2) were exposed to normoxia or hypoxia, and the conditioned medium (CM) of HepG2 was applied. Quantitative reverse transcription PCR (qRT-PCR) was implemented to analyze the miR-3156-5p profile. The cell counting kit-8 (CCK-8) assay and the colony formation experiment were conducted to measure cell proliferation, colony formation, and angiogenesis. Results: The results manifested that miR-3156-5p was up-regulated in HCC cells and endothelial cells under hypoxia, and up-regulating miR-3156-5p boosted HCC cell proliferation, endothelial cell angiogenesis, and HIF-1α/VEGF expression. Conclusions: miR-3156-5p activates the HIF-1α/VEGF pathway by hampering SOCS5, thereby enhancing the angiogenic potential of hypoxia-induced endothelial cells in HCC cells.

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Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

Cited by 39 publications

References 38 publications

METTL3-induced UCK2 m6A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway

METTL3-induced UCK2 m6A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway

Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea

miR-3156-5p Enhances Hypoxia-Induced Angiogenesis in Hepatocellular Carcinoma via Modulating the SOCS5/HIF-1α/VEGF Pathway

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